Can Pregnancy Help Scientists Better Understand Cancer?

Stvetomir Markovic knew something was different. Sometime around 2010, a fellow scientist at the Mayo Clinic had agreed to donate her healthy blood for use in the research laboratory where Markovic studies the interface between cancer and the immune system. In previous testing of the woman’s blood, her immune cells functioned normally. But then something changed, and nobody knew why.

“We thought our assays weren’t working,” recalls Markovic, a hematologist and oncologist whose research focuses on developing immunotherapies for melanoma and non-Hodgkin’s lymphoma. Or perhaps the reagents had expired, or the laboratory’s machines needed fine-tuning. For nearly a month, the team puzzled over the woman’s changing lab values. “At this point, she was quite visibly pregnant,” Markovic laughs, noting how obvious the answer seems in hindsight. “It finally dawned on me—what if it’s the pregnancy?”

Sensing that the question’s answer could have implications for his cancer research, Markovic decided to study cells of the placenta, the disk-shaped organ that develops during pregnancy and connects the mother’s blood supply with that of her fetus. In the eight years since then, Markovic and other researchers have discovered some remarkable similarities in how cancer cells and placental cells regulate the immune system. This knowledge may one day lead to better cancer detection and treatment. For now, though, researchers are focused on deciphering the underlying process—and answering a sobering question: Are the cells of death exploiting the mechanisms intended to promote the cells of life?

Typically, when the body senses a foreign substance such as a virus or a bacterium, it sends immune cells to attack the invader while also bolstering the immune system as a whole. Cancer cells are vulnerable to this kind of attack because they produce mutated proteins that the immune system may identify as foreign. But cancer cells can escape immune surveillance using a variety of techniques to disguise themselves.

Until recently, Markovic says, most scientists believed that outside of localized changes near the cancer cells, the immune system of cancer patients essentially functioned normally. But as a young researcher in the early 2000s, he wasn’t convinced this told the whole story. He tested that idea by comparing immune-cell activity in the blood of healthy people and cancer patients.

What he found was that cancer doesn’t merely disrupt the immune response around the tumor—it affects the entire system. One of his team’s early findings, published in 2011, was that tumors have high levels of a particular protein known to suppress the immune system and induce a state of system-wide chronic inflammation. He says in his experiments, the immune system “was totally unable to fight.” What’s more, it became increasingly protective of cancer cells. He wondered: “How could a tiny cancer cell cause such dysfunction across the whole body’s immune system?”

Markovic theorized that tumors train the immune system to tolerate their foreign protein, though he wasn’t sure how until the pregnant researcher’s blood got him thinking. Researchers already knew that a woman’s immune system changes during pregnancy. Perhaps these changes could help explain what happens during cancer.

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